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Introduction: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-stage kidney disease patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Vaccination on dialysis patients (DP) still remains challenging because of the variable response and a low seroconversion rate compared with healthy participants (HP). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of the dose and administration time. Methods: Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HP were evaluated by absolute quantification of IgG levels in the blood. Results: DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HP. While HP reached complete seroconversion within 10 days from the administration of a second dose, only 76% of DP were seropositive. After the booster dose, DP had a strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels. Discussion/Conclusion: These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since limited data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after the booster vaccine dose.

Atypical retinoids (AR) or retinoid-related molecules (RRMs) represent a promising class of antitumor compounds. Among AR, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (adarotene), has been extensively investigated. In the present work we report the results of our efforts to develop new adarotene-related atypical retinoids endowed also with POLA1 inhibitory activity. The effects of the synthesized compounds on cell growth were determined on a panel of human and hematological cancer cell lines. The most promising compounds showed antitumor activity against several tumor histotypes and increased cytotoxic activity against an adarotene-resistant cell line, compared to the parent molecule. The antitumor activity of a selected compound was evaluated on HT-29 human colon carcinoma and human mesothelioma (MM487) xenografts. Particularly significant was the in vivo activity of the compound as a single agent compared to adarotene and cisplatin, against pleural mesothelioma MM487. No reduction of mice body weight was observed, thus suggesting a higher tolerability with respect to the parent compound adarotene.

Hybrid molecules targeting simultaneously DNA polymerase α (POLA1) and histone deacetylases (HDACs) were designed and synthesized to exploit a potential synergy of action. Among a library of screened molecules, MIR002 and GEM144 showed antiproliferative activity at nanomolar concentrations on a panel of human solid and haematological cancer cell lines. In vitro functional assays confirmed that these molecules inhibited POLA1 primer extension activity, as well as HDAC11. Molecular docking studies also supported these findings. Mechanistically, MIR002 and GEM144 induced acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. Oral administration of these inhibitors confirmed their antitumor activity in in vivo models. In human non-small cancer cell (H460) xenografted in nude mice MIR002 at 50 mg/kg, Bid (qd × 5 × 3w) inhibited tumor growth (TGI = 61%). More interestingly, in POLA1 inhibitor resistant cells (H460-R9A), the in vivo combination of MIR002 with cisplatin showed an additive antitumor effect with complete disappearance of tumor masses in two animals at the end of the treatment. Moreover, in two human orthotopic malignant pleural mesothelioma xenografts (MM473 and MM487), oral treatments with MIR002 and GEM144 confirmed their significant antitumor activity (TGI = 72–77%). Consistently with recent results that have shown an inverse correlation between POLA1 expression and type I interferon levels, MIR002 significantly upregulated interferon-α in immunocompetent mice.

Context: The Global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has resulted in explosive patterns of transmission in most countries. Nasopharyngeal swabs were the specimen’s collection tools recommended for the diagnosis of SARS-CoV-2 infection, and for monitoring infection outbreaks in communities. Our objective was to report the quality and efficacy of unsupervised self-collected mid turbinate “dry FLOQSwabs” (MT FLOQSwabs) (56380CS01, Copan). There were 111 specimens collected for the study: 36 by health care personnel, from themselves, to verify the quality and efficacy of mid-turbinate swabs, 75 to compare and assess the diagnostic performance, among health care personnel, of nasopharyngeal swabs and self-collected mid-turbinate FLOQSwabs. A collection of 51 specimens was enrolled to define the efficacy of the Testami program (validation). Our analyses demonstrate that self-collected mid-turbinate dry swabs ensure an accuracy of 97.3%, as compared to the standard nasopharyngeal swabs collected by health care workers. Furthermore, the mid-turbinate FLOQSwabs can be stored without medium for six days at room temperature without affecting the molecular diagnosis of the SARS-CoV-2 virus infection. Self-collection of diagnostic specimens at home could offer an avenue to increase testing availability for SARS-CoV-2 infection without asking people to travel to a clinic or a laboratory, thus reducing people’s exposure to infection. Our findings demonstrate that unsupervised self-collection swabs, transported dry, are sensitive, practical and easy-to-use tools and should be considered for diagnosis of SARS-COV-2 and coronavirus disease 2019 (COVID-19) surveillance.